Tolerability and Safety of Multiple Dose Regimens of TRX4 Anti-CD3 Monoclonal Antibody in Type 1 Diabetes Mellitus

Conditions: Type I Diabetes Mellitus
MedDRA version: 8.1Level: LLTClassification code 10045228Term: Type I diabetes mellitus

Registration Number: EUCTR2006-003579-11-DE

Lead Sponsor: TolerRx, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

Inclusion Criteria

1) Subjects able to give informed consent
2) Men or women of any race, between 18 and 60 years old (inclusive), in good general health
3) Confirmed diagnosis of Type 1 Diabetes Mellitus, insulin-requiring, on a relatively stable insulin regimen for one month prior to initiating TRX4 dosing, with good metabolic control (HbA1c less than 8.5 %)
4) Less than 10 % weight loss due to Diabetes in the past six months
5) Positive for at least one Type 1 Diabetes Mellitus autoantibody, i.e. anti-GAD (glutamic acid decarboxylase), IA-2, or insulin autoantibody
6) Willingness to remain in the clinic for the inpatient portion of the study
7) Prescription medications must be stable for at least four weeks before the first dose of study drug
8) Female subjects must not be pregnant or lactating and either be surgically sterile, postmenopausal for at least one year, or using an acceptable method of contraception defined as oral, implanted, or transdermal contraceptive, plus one of the following barrier methods: diaphragm with spermicidal cream/jelly or use of a condom by sexual partner
9) Screen body-mass-index of less than 34
10) Negative PPD skin test at screen (may be reactive, but not positive)
11) No clinically significant abnormal laboratory values within one week of the first TRX4-dose
12) Negative Hepatitis-C antibody, Hepatitis-B surface antigen, Hepatitis-B core antibody
13) Negative HIV antibody and no risk factors for HIV infection
14) Seropositive for Epstein-Barr-Virus (EBV) with quantitative polymerase chain reaction of less than 10000 copies of EBV DNA / 1000000 lymphocytes
15) CD4+ lymphocyte counts must be within normal limit within 35 days prior to the first dose of TRX4.
16) Negative syphilis test.
17) Negative qualtitative urine drug or alcohol test at screen.
18) Other than T1DM, all organ systems must be free of significant disease and the subject cannot have undergone recent clinically significant surgery.
20) The investigator must judge all pre-admission vital signs, physical examination, laboratory, or any safety variables to be within normal limits or clinically insignificant.
21) Negative / below detectable limit serum rheumatoid factor (RF).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Subjects with a current or prior malignancy, other than non-melanoma skin cancer (subjects with more than 5 occurrences of non-melanoma skin cancer and the last occurrence within 3 months of study entry).
2) Subjects that have received a vaccine within 30 days before TRX4 dosing, OR anticipate requiring a vaccine within 14 days after the last dose of TRX4.
3) Subjects considering or have scheduled any surgeries during the Core Study.
4) Subject with any significant mental or physical illness within a one year period prior to the first dose, including a history of alcohol and/or drug abuse.
5) Subjects having donated plasma or blood within 30 days prior to the first dose of TRX4.
6) Subjects having used any investigational drugs within three months prior to the first dose of TRX4 or within the core study period.
7) Subjects with a history of anaphylactic reactions.
8) Subjects having experienced a significant systemic infection within three months before the first dose of TRX4.
9) Subjects who may, based on medical history, require treatment with systemic corticosteroids during the study.
10) Subjects thought to have an allergy or sensitivity to TRX4 or excipients based upon known allergies to compounds of a similar class, or which, in the opinion of the principal investigator, suggests an increased potential for an adverse hypersensitivity to TRX4.
11) Subjects having received any other anti-CD3 Mab at any time in the past (e.g., OKT3; ChAglyCD3; OKT3 ala-ala).
12) Subjects having undergone splenectomy.